foxo
D. melanogaster
forkhead box, sub-group O
What the model saw
Gene: foxo Organism: Drosophila melanogaster Known functions: forkhead box, sub-group O. DNA-binding transcription activator activity, RNA polymerase II-specific. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II transcription regulatory region sequence-specific DNA binding. protein binding. sequence-specific DNA binding.
View unredacted entry
forkhead box, sub-group O. DNA-binding transcription activator activity, RNA polymerase II-specific. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. RNA polymerase II transcription regulatory region sequence-specific DNA binding. protein binding. sequence-specific DNA binding.
Solver output
FOXO (Forkhead box, sub-group O) is a transcription factor that acts as the primary downstream effector of the insulin/IGF-1 signaling (IIS) pathway. When IIS is reduced, FOXO is dephosphorylated and translocates to the nucleus, where it activates RNA Pol II-dependent transcription of target genes involved in stress resistance, proteostasis, autophagy, and metabolism. In Drosophila, overexpression of dFOXO in the fat body extends lifespan, while loss of dFOXO shortens it. Its DNA-binding transcription activator activity drives expression of pro-longevity targets such as 4E-BP (Thor), superoxide dismutase, and autophagy genes, directly opposing the pro-aging effects of hyperactive IIS. This places dFOXO as a central node in the nutrient-sensing longevity axis, conserved from worms to mammals.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly identified foxo as pro_longevity with very high confidence (0.97). The mechanistic reasoning is excellent and accurate: FOXO is indeed the downstream effector of the insulin/IGF-1 signaling pathway in Drosophila, dephosphorylated when IIS is reduced, translocating to the nucleus to activate pro-longevity transcriptional targets. The specific examples cited (4E-BP/Thor, SOD, autophagy genes) are accurate. The fat body overexpression extending lifespan is a well-established finding. The mechanism class "deregulated_nutrient_sensing" is appropriate. This is a textbook example of a pro-longevity gene in Drosophila and the model handled it perfectly.
Raw API responses
solver
{
"reasoning": "FOXO (Forkhead box, sub-group O) is a transcription factor that acts as the primary downstream effector of the insulin/IGF-1 signaling (IIS) pathway. When IIS is reduced, FOXO is dephosphorylated and translocates to the nucleus, where it activates RNA Pol II-dependent transcription of target genes involved in stress resistance, proteostasis, autophagy, and metabolism. In Drosophila, overexpression of dFOXO in the fat body extends lifespan, while loss of dFOXO shortens it. Its DNA-binding transcription activator activity drives expression of pro-longevity targets such as 4E-BP (Thor), superoxide dismutase, and autophagy genes, directly opposing the pro-aging effects of hyperactive IIS. This places dFOXO as a central node in the nutrient-sensing longevity axis, conserved from worms to mammals.",
"confidence": 0.97,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) pathway",
"FOXO transcription factor network",
"autophagy and stress resistance gene regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified foxo as pro_longevity with very high confidence (0.97). The mechanistic reasoning is excellent and accurate: FOXO is indeed the downstream effector of the insulin/IGF-1 signaling pathway in Drosophila, dephosphorylated when IIS is reduced, translocating to the nucleus to activate pro-longevity transcriptional targets. The specific examples cited (4E-BP/Thor, SOD, autophagy genes) are accurate. The fat body overexpression extending lifespan is a well-established finding. The mechanism class \"deregulated_nutrient_sensing\" is appropriate. This is a textbook example of a pro-longevity gene in Drosophila and the model handled it perfectly.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}